Patients with chronic kidney disease (CKD) are at higher risk of developing CVD including atherosclerotic cardiovascular disease (ASCVD), compared to the general population, and this increased risk is unexplained by traditional risk factors for CVD. The role of genetically determined variants of key mediators of CVD under-explored. The Principal Investigator (PI) has designed a rigorous training program that will provide her with the necessary skills, experience and opportunities to develop into an independent investigator in the field of genetic epidemiology in relation to chronic kidney disease. She will obtain a Masters of Science in Clinical Care Research with special emphasis on genetic epidemiology, participate in projects utilizing a broad range of study designs for clinical research and carry out an original research project from its inception to completion. Her mentors have extensive experience in clinical and laboratory investigation of CKD and, ESRD, and in clinical and translational research in Nephrology. Transforming growth factor-beta (TGF-beta1) and Plasminogen activator inhibitor-1 (PAl-1) play key regulatory roles in atherogenesis and kidney disease progression, and interact with angiotensin II (All) and each other. The hypotheses to be investigated are that functionally relevant single nucleotide polymorphisms (SNP) in the promoter and coding regions of TGF-beta1 and in the promoter regions of PAl-1 contribute to cardiovascular risk in patients with CKD. The Specific Aims are to 1) determine the frequency of SNP's of TGF-beta1 and PAl-1 in patients with CKD 2) examine their relationship to plasma levels of TGF-beta1 and PAl-1 respectively and 3) Evaluate their relationship to the prevalence and progression of ASCVD, as measured by carotid ultrasound intima-media thickness, ankle-brachial index and clinical ASCVD. The research project is achievable and promises to provide new insights into the importance of genetic factors as novel markers of cardiovascular risk. The results may help identify patients who could benefit from maximal All blockade or anti-fibrogenic therapies. The PI has assembled a team of scientists to assist in the conduct of the project and convened an internal and external scientific advisory committee to monitor her progress. The proposed training program and research project will prepare her for a career as an independent investigator.